Chapter 10 Flashcards
Caffeine is antagonist for ____ receptor
adenosine
Bacterial Quorum Sensing
Sense # organisms in population.
Diffuse through cell membrane, bind to intracellular receptors, effect change in gene receptors
What do kinases do?
Gene expression and metabolic activity
limits of signaling (6)
- amplified intracellularly (stepwise)
- regulation
- location: cytosol/nuclear
- branching: redundancy/cancellation
- signal termination (2nd messengers short lived)
- desensitization
PKA
Ser/Thr kinase
Activation up when phosphorylated (phospho-Thr)
When activated,
Phospho-Thr —-> Arg (+, arginine)
Asp (-, asparagine) near 3rd phosphate and substrate
What 2 things activate PKA?
Allosteric activation by cAMP
Priming phospho-thr
Insulin effects
increases glycogen synthesis
decreases phosphorylation
opposite PKA, PKA gives fuel mobilization signal
Arrestin
Docking protein. When GPCR bound, kinase phosphorylates it. Arrestin recognizes phosphorylated form of G protein.
G protein docking and thus the signal
Arrestin removed by dephosphorylated.
Where is PIP2 cleaved?
C3
What does IP3 activate?
Calcium released –> PKB/Akt
What does DAG activate?
PKC
What 2 things activate PKC?
Requires priming at Thr?
DAG causes dock near membrane and conformation change
Calmodulin
Regulates calcium
Activates or inhibits target proteins
Bends in 1/2 to grasp target
Binds 2x calcium ions
Cross-Talk between signaling pathways (due to intracellular components) name examples
PLC activated by PTKs lipid phosphatases
Sphingomyelinases release sphingosine & ceramide (activate 2nd messengers)
Ceramide = 2nd messenger
Sphingosine-1-phosphate= intra/extracellular signal (-PLC, +GPCRs, aker export by ABC transport) must be exported by ABC but then can diffuse to modify GPCRs
Ras Pathway
- RTK+ Ras* GDP inactive
- Ligand binds, RTK phosphorylates
- Adaptor proteins connect Ras to RTK/phosphates
- Induced Ras to release GDP and bind to GTP
- Activates Kinase
What does Ras target?
Nuclear proteins, which alter gene expression= transcription factors
What limits Ras signaling
GTPase activity
What reverses kinase effects ?
phosphatases
Anticancer drugs
inhibit kinases, stop uninhibited growth
In lipid hormone signaling, ___ binds to DNA and initiates transcription.
Hormone responsive element (HRE)
What eicosanoid signaling molecule enzyme converts arachnodonate to prostaglandin H2.
Cyclooxygenase
Eicosanoids produced when ________activated by phosphorylation and by presence of Ca2+.
phospholipase A2
Why is ligand binding reversible
non-covalent
Kinase
enzyme that transfers a phosphoryl group from ATP to another molecule.
GPCR structure
7 transmembrane alpha helices
Pal @ cys
Ligand binding: helical core and extracellular loops
Beta blockers
Block beta2-Aderngic
Treat high bp
how does intrinsic GTPase activity limit a G protein?
Bound GTP — > GDP
____ is allosteric activator of kinase
cAMP
When threonine on PKA not phosphorylated,
active site blocked
Arrestin has ___ residues which bind to phosphoryl group.
Lys (+) and Arg (arginine, +)
Arrestin uses endocytosis
What changes loop blocking PKC active site?
noncovalent binding with DAG
Phosphoinositide signaling pathway regulation:
- Lipid phosphatases: remove phosphoryl groups from PIP2
2. Sphingosine inhibits PLC (see above)
What stops Ras signaling?
Proteins that enhance GTPase activity so it returns to inactive GDP bound form
Phosphatases reverse some kinases.
Tyrosine kinases can cross-talk (see book for additional notes)
Lipids carried in bloodstream by specific carrier protein or ___, all purpose binding protein.
albumin
Lipid Receptor
2 zinc fingers: cross links formed by 4 cysteine residues interacting with 4 zinc ions.
Once lipid ligand binds, moves to ____ and binds to HRE, which all have ____
nucleus
6-bp sequences separated by a few bp
Are lipid signals long lasting?
no short range, degraded quickly because unstable and hydrophobic
